scholarly journals Coordinated changes across the O 2 transport pathway underlie adaptive increases in thermogenic capacity in high-altitude deer mice

2020 ◽  
Vol 287 (1927) ◽  
pp. 20192750 ◽  
Author(s):  
Kevin B. Tate ◽  
Oliver H. Wearing ◽  
Catherine M. Ivy ◽  
Zachary A. Cheviron ◽  
Jay F. Storz ◽  
...  
Keyword(s):  
High Altitude ◽  
Complex Traits ◽  
Deer Mice ◽  
Transport Pathway ◽  
Physiological Mechanisms ◽  
Critical Determinant ◽  
In Captivity ◽  
Low Altitude ◽  
Hypoxia Acclimation ◽  
Thermogenic Capacity

Animals native to the hypoxic and cold environment at high altitude provide an excellent opportunity to elucidate the integrative mechanisms underlying the adaptive evolution and plasticity of complex traits. The capacity for aerobic thermogenesis can be a critical determinant of survival for small mammals at high altitude, but the physiological mechanisms underlying the evolution of this performance trait remain unresolved. We examined this issue by comparing high-altitude deer mice ( Peromyscus maniculatus ) with low-altitude deer mice and white-footed mice ( P. leucopus ). Mice were bred in captivity and adults were acclimated to each of four treatments: warm (25°C) normoxia, warm hypoxia (12 kPa O 2 ), cold (5°C) normoxia or cold hypoxia. Acclimation to hypoxia and/or cold increased thermogenic capacity in deer mice, but hypoxia acclimation led to much greater increases in thermogenic capacity in highlanders than in lowlanders. The high thermogenic capacity of highlanders was associated with increases in pulmonary O 2 extraction, arterial O 2 saturation, cardiac output and arterial–venous O 2 difference. Mechanisms underlying the evolution of enhanced thermogenic capacity in highlanders were partially distinct from those underlying the ancestral acclimation responses of lowlanders. Environmental adaptation has thus enhanced phenotypic plasticity and expanded the physiological toolkit for coping with the challenges at high altitude.

scholarly journals Evolved changes in breathing and CO2 sensitivity in deer mice native to high altitudes

2018 ◽  
Vol 315 (5) ◽  
pp. R1027-R1037 ◽  
Author(s):  
Catherine M. Ivy ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
Deer Mice ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
In Captivity ◽  
Generation Progeny ◽  
First And Second Generation ◽  
Hypoxia Acclimation

We examined the control of breathing by O2 and CO2 in deer mice native to high altitude to help uncover the physiological specializations used to cope with hypoxia in high-altitude environments. Highland deer mice ( Peromyscus maniculatus) and lowland white-footed mice ( P. leucopus) were bred in captivity at sea level. The first and second generation progeny of each population was raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa O2, simulating hypoxia at ~4,300 m) for 6–8 wk. Ventilatory responses to poikilocapnic hypoxia (stepwise reductions in inspired O2) and hypercapnia (stepwise increases in inspired CO2) were then compared between groups. Both generations of lowlanders appeared to exhibit ventilatory acclimatization to hypoxia (VAH), in which hypoxia acclimation enhanced the hypoxic ventilatory response and/or made the breathing pattern more effective (higher tidal volumes and lower breathing frequencies at a given total ventilation). In contrast, hypoxia acclimation had no effect on breathing in either generation of highlanders, and breathing was generally similar to hypoxia-acclimated lowlanders. Therefore, attenuation of VAH may be an evolved feature of highlanders that persists for multiple generations in captivity. Hypoxia acclimation increased CO2 sensitivity of breathing, but in this case, the effect of hypoxia acclimation was similar in highlanders and lowlanders. Our results suggest that highland deer mice have evolved high rates of alveolar ventilation that are unaltered by exposure to chronic hypoxia, but they have preserved ventilatory sensitivity to CO2.

scholarly journals Distinct Mechanisms Underlie Developmental Plasticity and Adult Acclimation of Thermogenic Capacity in High-Altitude Deer Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Catherine M. Ivy ◽  
Haley Prest ◽  
Claire M. West ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Developmental Plasticity ◽  
Adult Life ◽  
Lung Ventilation ◽  
Deer Mice ◽  
Life Stages ◽  
Physiological Plasticity ◽  
Physiological Mechanisms ◽  
In Captivity ◽  
The Relationship

Developmental plasticity can elicit phenotypic adjustments that help organisms cope with environmental change, but the relationship between developmental plasticity and plasticity in adult life (e.g., acclimation) remains unresolved. We sought to examine developmental plasticity and adult acclimation in response to hypoxia of aerobic capacity (V̇O2max) for thermogenesis in deer mice (Peromyscus maniculatus) native to high altitude. Deer mice were bred in captivity and exposed to normoxia or one of four hypoxia treatments (12 kPa O2) across life stages: adult hypoxia (6–8 weeks), post-natal hypoxia (birth to adulthood), life-long hypoxia (before conception to adulthood), and parental hypoxia (mice conceived and raised in normoxia, but parents previously exposed to hypoxia). Hypoxia during perinatal development increased V̇O2max by a much greater magnitude than adult hypoxia. The amplified effect of developmental hypoxia resulted from physiological plasticity that did not occur with adult hypoxia – namely, increases in lung ventilation and volume. Evolved characteristics of deer mice enabled developmental plasticity, because white-footed mice (P. leucopus; a congener restricted to low altitudes) could not raise pups in hypoxia. Parental hypoxia had no persistent effects on V̇O2max. Therefore, developmental plasticity can have much stronger phenotypic effects and can manifest from distinct physiological mechanisms from adult acclimation.

scholarly journals Acclimation to hypoxia increases carbohydrate use during exercise in high-altitude deer mice

2017 ◽  
Vol 312 (3) ◽  
pp. R400-R411 ◽  
Author(s):  
Daphne S. Lau ◽  
Alex D. Connaty ◽  
Sajeni Mahalingam ◽  
Nastashya Wall ◽  
Zachary A. Cheviron ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Altitude ◽  
Muscle Metabolism ◽  
Deer Mice ◽  
Metabolic Enzyme ◽  
Acid Oxidation ◽  
Fuel Use ◽  
Muscle Gene Expression ◽  
Low Altitude ◽  
Hypoxia Acclimation

The low O2 experienced at high altitude is a significant challenge to effective aerobic locomotion, as it requires sustained tissue O2 delivery in addition to the appropriate allocation of metabolic substrates. Here, we tested whether high- and low-altitude deer mice ( Peromyscus maniculatus) have evolved different acclimation responses to hypoxia with respect to muscle metabolism and fuel use during submaximal exercise. Using F1 generation high- and low-altitude deer mice that were born and raised in common conditions, we assessed 1) fuel use during exercise, 2) metabolic enzyme activities, and 3) gene expression for key transporters and enzymes in the gastrocnemius. After hypoxia acclimation, highland mice showed a significant increase in carbohydrate oxidation and higher relative reliance on this fuel during exercise at 75% maximal O2 consumption. Compared with lowland mice, highland mice had consistently higher activities of oxidative and fatty acid oxidation enzymes in the gastrocnemius. In contrast, only after hypoxia acclimation did activities of hexokinase increase significantly in the muscle of highland mice to levels greater than lowland mice. Highland mice also responded to acclimation with increases in muscle gene expression for hexokinase 1 and 2 genes, whereas both populations increased mRNA expression for glucose transporters. Changes in skeletal muscle with acclimation suggest that highland mice had an increased capacity for the uptake and oxidation of circulatory glucose. Our results demonstrate that highland mice have evolved a distinct mode of hypoxia acclimation that involves an increase in carbohydrate use during exercise.

Low P50 in deer mice native to high altitude

1985 ◽  
Vol 58 (1) ◽  
pp. 193-199 ◽  
Author(s):  
L. R. Snyder
Keyword(s):  
High Altitude ◽  
Significant Negative Correlation ◽  
Deer Mice ◽  
Hypoxic Stress ◽  
Hemoglobin Saturation ◽  
Partial Pressures ◽  
Theoretical Predictions ◽  
Low Altitude ◽  
The Difference

Whereas it is widely believed that animals native to high altitude show lower O2 partial pressures at 50% hemoglobin saturation (P50) than do related animals native to low altitude, that “fact” has not been well documented. Consequently, P50 at pH 7.4, PCO2(7.4), the CO2 Bohr effect, and the buffer slope (delta log PCO2/delta pH) were determined via the mixing technique in Peromyscus maniculatus native to a range of altitudes but acclimated to 340 or 3,800 m. PCO2(7.4) and buffer slope were substantially lower at high altitude. The change in P50(7.4) between acclimation altitudes was minimal (0.8% increase at 3,800 m), because of counterbalancing changes in PCO2, 2,3-diphospho-D-glycerate concentration, and perhaps other factors. At both acclimation altitudes there was a highly significant negative correlation between P50(7.4) and native altitude. Since pH in vivo probably increases slightly at high altitude, the data on P50 corrected to pH 7.4 are probably underestimates of the difference in in vivo P50 at low vs. high altitude. Hence these results corroborate theoretical predictions that low P50 is advantageous under severe hypoxic stress.

scholarly journals Plasticity of non-shivering thermogenesis and brown adipose tissue in high-altitude deer mice

2021 ◽  
Author(s):  
Soren Z. Coulson ◽  
Cayleih E. Robertson ◽  
Sajeni Mahalingam ◽  
Grant B. McClelland
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Altitude ◽  
Heat Production ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Deer Mice ◽  
Brown Adipose ◽  
Hypoxia Acclimation ◽  
Shivering Thermogenesis

High altitude environments challenge small mammals with persistent low ambient temperatures that require high rates of aerobic heat production in face of low O2 availability. An important component of thermogenic capacity in rodents is non-shivering thermogenesis (NST) mediated by uncoupled mitochondrial respiration in brown adipose tissue (BAT). NST is plastic, and capacity for heat production increases with cold acclimation. However, in lowland native rodents, hypoxia inhibits NST in BAT. We hypothesize that highland deer mice (Peromyscus maniculatus) overcome the hypoxic inhibition of NST through changes in BAT mitochondrial function. We tested this hypothesis using lab born and raised highland and lowland deer mice, and a lowland congeneric (P. leucopus), acclimated to either warm normoxia (25°C, 760 mmHg) or cold hypoxia (5°C, 430 mmHg). We determined the effects of acclimation and ancestry on whole-animal rates of NST, the mass of interscapular BAT (iBAT), and uncoupling protein (UCP)-1 protein expression. To identify changes in mitochondrial function, we conducted high-resolution respirometry on isolated iBAT mitochondria using substrates and inhibitors targeted to UCP-1. We found that rates of NST increased with cold hypoxia acclimation but only in highland deer mice. There was no effect of cold hypoxia acclimation on iBAT mass in any group, but highland deer mice showed increases in UCP-1 expression and UCP-1 stimulated mitochondrial respiration in response to these stressors. Our results suggest that highland deer mice have evolved to increase the capacity for NST in response to chronic cold hypoxia, driven in part by changes in iBAT mitochondrial function.

Lipid Oxidation during Thermogenesis in High-Altitude Deer Mice (Peromyscus maniculatus)

2021 ◽  
Author(s):  
Sulayman Aslan Lyons ◽  
Kevin B Tate ◽  
Kenneth Collins Welch ◽  
Grant B. McClelland
Keyword(s):  
Lipid Oxidation ◽  
Palmitic Acid ◽  
High Altitude ◽  
Deer Mice ◽  
Acid Oxidation ◽  
Cold Environments ◽  
Oxidation Rates ◽  
Low Altitude ◽  
Land Mammal ◽  
Specific Lipid

When at their maximum thermogenic capacity (cold-induced V̇O2max), small endotherms reach levels of aerobic metabolism as high, or even higher, than running V̇O2max. How these high rates of thermogenesis are supported by substrate oxidation is currently unclear. The appropriate utilization of metabolic fuels that could sustain thermogenesis over extended periods may be important for survival in cold environments, like high altitude. Previous studies show that high capacities for lipid use in high-altitude deer mice may have evolved in concert with greater thermogenic capacities. The purpose of this study was to determine how lipid utilization at both moderate and maximal thermogenic intensities may differ in high- and low- altitude deer mice, and strictly low-altitude white-footed mice. We also examined the phenotypic plasticity of lipid use after acclimation to cold hypoxia (CH), conditions simulating high altitude. We found that lipids were the primary fuel supporting both moderate and maximal rates of thermogenesis in both species of mice. Lipid oxidation increased 3-fold in mice from 30oC to 0oC, consistent with increases in oxidation of [13C]-palmitic acid. CH acclimation led to an increase in [13C]-palmitic acid oxidation at 30oC but did not affect total lipid oxidation. Lipid oxidation rates at cold-induced V̇O2max were two- to four-fold those at 0oC and increased further after CH acclimation, especially in high-altitude deer mice. These are the highest mass-specific lipid oxidation rates observed in any land mammal. Uncovering the mechanisms that allow for these high rates of oxidation will aid our understanding of the regulation of lipid metabolism.

scholarly journals Individual variation in thermogenic capacity affects above-ground activity of high-altitude Deer Mice

2006 ◽  
Vol 20 (1) ◽  
pp. 97-104 ◽  
Author(s):  
M. W. SEARS ◽  
J. P. HAYES ◽  
C. S. O'CONNOR ◽  
K. GELUSO ◽  
J. S. SEDINGER
Keyword(s):  
High Altitude ◽  
Individual Variation ◽  
Deer Mice ◽  
Thermogenic Capacity

scholarly journals Regulatory changes contribute to the adaptive enhancement of thermogenic capacity in high-altitude deer mice

2012 ◽  
Vol 109 (22) ◽  
pp. 8635-8640 ◽  
Author(s):  
Z. A. Cheviron ◽  
G. C. Bachman ◽  
A. D. Connaty ◽  
G. B. McClelland ◽  
J. F. Storz
Keyword(s):  
High Altitude ◽  
Deer Mice ◽  
Regulatory Changes ◽  
Adaptive Enhancement ◽  
Thermogenic Capacity

scholarly journals Life Ascending: Mechanism and Process in Physiological Adaptation to High-Altitude Hypoxia

2019 ◽  
Vol 50 (1) ◽  
pp. 503-526 ◽  
Author(s):  
Jay F. Storz ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Environmental Conditions ◽  
Physiological Adaptation ◽  
Aerobic Performance ◽  
Cardiorespiratory System ◽  
Transport Pathway ◽  
Altitudinal Variation ◽  
Air Breathing ◽  
High Altitude Natives ◽  
Low Altitude

To cope with the reduced availability of O2 at high altitude, air-breathing vertebrates have evolved myriad adjustments in the cardiorespiratory system to match tissue O2 delivery with metabolic O2 demand. We explain how changes at interacting steps of the O2 transport pathway contribute to plastic and evolved changes in whole-animal aerobic performance under hypoxia. In vertebrates native to high altitude, enhancements of aerobic performance under hypoxia are attributable to a combination of environmentally induced and evolved changes in multiple steps of the pathway. Additionally, evidence suggests that many high-altitude natives have evolved mechanisms for attenuating maladaptive acclimatization responses to hypoxia, resulting in counter-gradient patterns of altitudinal variation for key physiological phenotypes. For traits that exhibit counteracting environmental and genetic effects, evolved changes in phenotype may be cryptic under field conditions and can only be revealed by rearing representatives of high- and low-altitude populations under standardized environmental conditions to control for plasticity.

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